Pneumocystis carinii Pneumonia in HIV-negative patients with haematologic disease

Summary Since 1990,Pneumocystis carinii pneumonia (PCP) was diagnosed in 15 adult HIV-negative haematologic patients in our hospital. None of them had received PCP prophylaxis. All except one had been treated with prednisone. Symptoms usually started after stopping or tapering. In six patients the diagnosis of PCP was delayed because of confounding bacterial isolates from blood, sputum or urine leading to unsuccessful antibiotic treatment. PCP was diagnosed by demonstrating pneumocysts in bronchoalveolar lavage fluid. In four patients additional fungal or viral pathogens were identified. The infections were not clustered. The patients were treated with co-trimoxazole and, in case of a pO₂<60 mmHg, with prednisone. Three patients died (20%); they all had a coinfection with cytomegalovirus and/or aspergillus. The others recovered completely. There were no relapses. Primary PCP prophylaxis should be considered in patients with lympho-proliferative disease and exposure to prednisone.     

Antibody responses to a major Pneumocystis carinii antigen in human immunodeficiency virus-infected patients with and without P. carinii pneumonia.

Antibody responses to a major purified human Pneumocystis carinii surface antigen (gp95) were determined by ELISA in human immunodeficiency virus (HIV)-infected patients. Serum IgG directed against gp95 was measured in 129 consecutive HIV-infected patients who underwent bronchoscopy for evaluation of pulmonary symptoms. Significantly more patients with P. carinii pneumonia (PCP) had detectable antibodies compared with HIV-infected patients without PCP and with HIV-negative controls (50 [66%] of 76 vs. 18 [34%] of 53 and 7 [35%] of 20, respectively; P less than .001), and the level of antibody response was higher (mean optical density ratio: 0.6 vs. 0.23 and 0.2, respectively; P less than .01). Changes in antibody response were investigated in 78 patients for whom serial serum samples taken around the time of bronchoscopy were available. Of the 47 patients with verified PCP, 20 (43%) mounted an antibody response, compared with only 1 (3%) of 31 patients without PCP (P less than .001). This patient had PCP on the basis of clinical criteria, including response to therapy. Thus, despite severe immunosuppression, a proportion of HIV-infected patients with PCP can mount a specific IgG-mediated antibody response to P. carinii.     

Pneumocystis carinii pneumonia in patients with connective tissue disease.

Four patients with PCP complicating a CTD are described. Rising serum lactate dehydrogenase levels were documented during an asymptomatic period associated with corticosteroid dosage tapering, weeks prior to the development of acute pulmonary symptoms. The diagnosis of PCP was established by FOB in each patient.     

Pneumocystis carinii pneumonia among patients with neoplastic disease.

Pneumocystis carinii pneumonia (PCP) emerged in the 1980s as the most common opportunistic infection among patients with the acquired immunodeficiency syndrome (AIDS). Because of this, the presentation and clinical course of PCP has become well-known to many physicians. However, PCP continues to occur among patients not infected with the human immunodeficiency virus, generally those who receive immunosuppressive therapy as treatment for neoplastic disease. A review from Memorial Sloan-Kettering Cancer has shown that a new group of patients, those receiving corticosteroid therapy for brain neoplasm, are also at risk for the development of PCP and should receive PCP prophylaxis. Previously defined patient groups--people with acute lymphocytic leukemia or allogeneic bone marrow transplantation--also should continue to receive prophylaxis. In addition, the clinical course and outcome of patients with neoplastic disease who develop PCP may differ from those with AIDS and PCP: the disease may be much more fulminant among patients with neoplastic disease, and the mortality rate much higher, approaching 50% in the Memorial Sloan-Kettering Cancer Center series. Wider use of prophylaxis should decrease the frequency of this disease, whereas prompt initiation of therapy in patients with a compatible syndrome should help to improve mortality rates.     

Polyamine metabolism in Pneumocystis carinii

Alpha-difluoromethylornithine (DFMO) is being used to treat Pneumocystis carinii pneumonia despite a lack of in vitro evidence supporting its antipneumocystis activity. DFMO is a specific inhibitor of ornithine decarboxylase, the rate-limiting enzyme of polyamine biosynthesis. To investigate polyamine metabolism in P. carinii, extracts of the organism were analyzed for polyamine content and ornithine decarboxylase activity, and [3H]ornithine and [14C]arginine incorporation into polyamines during short-term culture was determined. P. carinii extracts contained putrescine and spermidine in a ratio of 0.17:1; traces of spermine were detected. Although ornithine decarboxylase activity was not detected, P. carinii incorporated ornithine and arginine into putrescine and spermidine but not into spermine, suggesting that the spermine detected derived from contaminating host cells. Uninfected rat lung incorporated ornithine minimally. Pentamidine, DFMO, and alpha-monofluoromethyldehydroornithine methyl ester inhibited ornithine incorporation by up to 86% at clinically achievable concentrations. These data provide a rationale for using polyamine synthesis antagonists in P. carinii pneumonia and a method for screening antipneumocystis drugs in vitro.     

Pneumocystis carinii pneumonia in pregnancy

OBJECTIVE: To report five new cases of Pneumocystis carinii pneumonia (PCP) and to review and analyze the existing reports on the subject. METHOD: Five new cases of PCP during pregnancy are described. The cases, case series, and related articles on the subject in the English language were identified through a comprehensive MEDLINE search and reviewed. RESULTS: More than 80% of women with AIDS are of reproductive age, and PCP is the most common cause of AIDS-related death in pregnant women in the United States. Among 22 reviewed cases, the mortality rate was 50% (11 of 22 patients), which is higher than that usually reported for HIV-infected individuals with PCP. Respiratory failure developed in 13 patients (59%), and mechanical ventilation was therefore required, and the survival rate in patients requiring mechanical ventilation was 31%. Maternal and fetal outcomes were better in cases of PCP during the third trimester of the pregnancy. A variety of treatment regimens were used, including sulfamethoxazole-trimethoprim (SXT) alone or in combination with pentamidine, steroids, and eflornithine. The survival rate in patients treated with SXT alone was 71% (5 of 7 patients) and for those treated with SXT and steroids was 60% (3 of 5 patients), with an overall survival rate in both groups of 66.6% (8 of 12 patients). CONCLUSION: PCP has a more aggressive course during pregnancy, with increased morbidity and mortality. Maternal and fetal outcomes remain dismal. Treatment with SXT, compared to other therapies, may result in an improved outcome. Withholding appropriate PCP prophylaxis may adversely affect maternal and fetal outcomes.     

Serologic responses to somatic O and colonization-factor antigens of enterotoxigenic Escherichia coli in travelers.

To improve the retrospective diagnoses of enterotoxigenic Escherichia coli (ETEC) as a cause of travelers' diarrhea, as well as to determine the presence of colonization-factor antigens in these infections, a study of serologic responses to antigens of ETEC was done. Paired sera from 60 United States students in Cholula, Puebla, Mexico, were analyzed for rises in titer of antibody to heat-labile toxin, eight somatic antigen O serogroups associated with ETEC, and two colonization-factor antigens, CFA/I and CFA/II. Only 9% had a response to O antigens, while 20% had responses to the colonization-factor antigens. Response to the colonization-factor antigens correlated significantly with response to the heat-labile toxin and with culture evidence of ETEC infection. Serologic studies confirmed that colonization-factor antigen has a role in naturally acquired cases of travelers' diarrhea and that it can be used as an additional determinant of infection with ETEC.     

妊娠期大鼠对卡氏肺孢子菌的易感性研究

目的研究妊娠期大鼠对卡氏肺孢子菌（Pneumocystiscarinii,PC）的易感性,为妇女孕期保健及优生优育提供参考。方法采用皮下注射地塞米松的方法建立大鼠肺孢子菌肺炎（pneumocystispneumonia,PCP）模型,作为环境中Pc的感染来源。于实验的第6周处死2只PCP大鼠,取肺组织印片,用改良四胺银（GMS）染色,镜检Pc的感染情况。妊娠组、非妊娠组大鼠各取10只,于实验的第6周末将鼠笼置于PCP模型大鼠的鼠笼两侧,实验第7、8、9周分别取3只、3只和4只妊娠组及非妊娠组大鼠,乙醚麻醉下处死并取肺组织,提取DNA,PCR扩增Pc的mtI。SUrRNA。结果PCP模型组大鼠肺印片GMS染色后油镜下观察,可见大量Pc包囊,证明PCP模型建立成功。PCR扩增妊娠组8只大鼠Pc阳性,感染率为80．00％（8／10）;非妊娠组6只大鼠Pc阳性,感染率60．O¨0％（6／10）。经Fisher确切概率法检验,两组大鼠的Pc感染率差异无统计学意义（P〉0．05）。结论健康妊娠期大鼠对外源性Pc普遍易感,但感染率与非妊娠女鼠无明显善别．     

Pneumocystis carinii infection in non-AIDS patients

Infection with the opportunist fungus Pneumocystis carinii remains a significant cause of morbidity and mortality in non-HIV-infected individuals immunosuppressed by a wide range of malignancies, transplantation and inflammatory conditions. Glucocorticoid use appears to be an independent risk factor for the development of Pneumocystis carinii pneumonia. Transmission from infected to susceptible patients may occur, albeit infrequently. A diagnosis of Pneumocystis carinii pneumonia may be achieved in the majority of cases by DNA detection using polymerase chain reaction on oropharyngeal mouth washes.     

Pneumocystis carinii infections in transplant recipients

Pneumocystis carinii is an organism of uncertain taxonomy that causes diffuse pneumonitis in malnourished infants and immunocompromised hosts. In transplant recipients, the infection most commonly presents from 2 to 6 months after transplantation with symptoms of dyspnea, fever, and dry cough lasting from a few days to a few weeks. A diagnosis is most readily and safely achieved by examination of material obtained by bronchoalveolar lavage for cyst forms of the organism. The therapy of choice is intravenous trimethoprim-sulfamethoxazole. Patients allergic to sulfa drugs are usually given parenteral pentamadine. Prophylaxis with oral trimethoprim-sulfamethoxazole is able to prevent pneumonia due to P carinii and is recommended for most transplant recipients, although the lowest effective dose and the optimal duration of therapy have not been determined. The currently high level of interest in this pathogen, stimulated by the epidemic of acquired immunodeficiency syndrome, should foster research that will increase our understanding and enhance our control over this pathogen.     

Development of murine monoclonal antibodies to Pneumocystis carinii

Relatively little is known about the antigenic structure of Pneumocystis carinii and the immunopathogenesis of pneumonitis caused by P. carinii. To begin to define the antigenic character of the surface of this organism, we have produced murine monoclonal antibodies that react with the surface of P. carinii (obtained from rats), as detected by immunofluorescence and immunoelectron microscopy. Immunoblot analysis revealed that the six antibodies described in this report bound an antigen with an apparent molecular mass of 90,000-95,000 daltons. Although all six monoclonal antibodies bound P. carinii obtained from rats, only one (5E12) was also able to bind P. carinii obtained from rabbits, ferrets, and a human; this result demonstrated that isolates of P. carinii obtained from different species are not antigenically identical.